Magnetisation Transfer Ratio
Measuring myelin repair in multiple sclerosis with MRI
BACKGROUND
Myelin is the protective sheath surrounding nerve fibres in the brain and spinal cord, allowing electrical signals to travel efficiently and rapidly through the nervous system. In multiple sclerosis (MS), the immune system attacks this myelin, leaving nerve fibres unprotected and vulnerable to degeneration. Although current MS disease-modifying treatments are highly effective at reducing inflammation and relapse activity, they do not directly repair this damage. Promoting remyelination, the process by which myelin is regenerated, is one of our major research aims.
One challenge lies in detecting whether remyelination is actually occurring within the brain. Clinical improvement may take years to emerge, and conventional MRI scans often do not capture the subtle biological changes associated with repair over shorter time periods. More sensitive imaging biomarkers that can detect remyelination are therefore needed. Our group collaborate closely with Professor Declan Chard's group at UCL, who are world leading experts in myelin imaging.
MAGNETISATION TRANSFER RATIO (MTR)
Magnetisation transfer ratio (MTR) is an advanced MRI technique that is sensitive to interactions between water and macromolecules within brain tissue, particularly myelin. Unlike standard MRI sequences, MTR provides information about the relative preservation of myelin content. Areas with lower MTR values are generally associated with greater tissue injury and demyelination, while increases in MTR over time can reflect remyelination and increased myelin content.
In recent years, MTR has emerged as an important imaging biomarker of remyelination, particularly within clinical trials. MTR has allowed us to measure the response to remyelinating medicines, uncovering extra layers of complexity in particular the differences in myelin repair between and within lesions.
MTR IN REMYELINATION TRIALS
Our group has used MTR in both our remyelination trials, CCMR-One and CCMR-Two. In CCMR-One, MTR analyses demonstrated that remyelination is heterogeneous, varying according to both lesion location and spatial components, with stronger repair signals observed within grey matter lesions and at the rim of lesions (as compared to their core). These suggest that some tissue regions may retain a greater capacity for repair than others, and that this potential may depend on lesion location, baseline damage, age and underlying tissue integrity.
Using advanced lesion-level analyses centred around changes in MTR, we are now investigating how remyelination differs across distinct tissue and lesion areas within the CCMR2 cohort. This allows us to investigate not only whether metformin and clemastine are capable of promoting remyelination, but where that repair may be occurring, and in turn which tissues have the greatest capacity for recovery.
We have also begun to explore how MTR-based measures of remyelination relate to broader measures of brain health, including MRI-derived brain age, and we are now extending these approaches within CCMR-Two.
As new remyelinating therapies continue to emerge, refining sensitive imaging biomarkers is becoming increasingly important for early-stage clinical trials. Our work focuses on combining MTR with other complementary measures of tissue function and neurodegeneration in MS, including visual evoked potentials, eye tracking, volumetric MRI and blood biomarkers, to develop a more complete understanding of myelin repair and neuroprotection in multiple sclerosis.